Nanofiber 'monorails' ferry brain tumors to their death

Glioblastoma is the deadliest form of brain cancer, and one reason it is difficult to
treat is because tumor cells spread to other parts of the brain by following nerve fibers and
blood vessels. Now, using nanofiber "monorails," biomedical engineers have found a way to
hijack this migratory feature and lure the malignant cells elsewhere.

The idea is to entice the migrating cancer cells toward a more accessible location where they
can be killed. This could be outside the brain, for instance.

Another option, for example, could be to move tumors from inoperable locations to somewhere
surgeons can remove them more easily.

While it is unlikely such a method will remove the cancer completely, the hope is one day a
deadly disease may be transformed into one that is treated more like a chronic one.

When they tested the method in animals, the researchers found it reduced the size of brain
tumors.

They report their work in the journal Nature Materials.

Each year in the US, around 10,000 people are diagnosed with glioblastoma. They are currently
treated with chemotherapy, radiation and surgery, but even when they receive all three, patients
rarely live more than 18 months after diagnosis.

Cancer cells latch onto man-made nanofibers and 'ride them like a monorail'

Nanofibers are so-called because they are extremely thin, in this case, about half the
thickness of human hair, and on a scale compatible with nerve fibers and blood vessels. Lead
researcher Ravi Bellamkonda, professor and chair of the Wallace H. Coulter Department of
Biomedical Engineering at Georgia Tech and Emory University in Atlanta, explains:

"We have designed a polymer thin film nanofiber that mimics the structure of nerves and blood
vessels that brain tumor cells normally use to invade other parts of the brain."

"The cancer cells normally latch onto these natural structures and ride them like a monorail
to other parts of the brain," he continues. "By providing an attractive alternative fiber, we
can efficiently move the tumors along a different path to a destination that we choose."

He adds that an attractive feature of such a method could be that it offers an alternative to drug
and radiation treatments:

"There are no drugs entering the blood stream and circulating in the brain to harm healthy
cells. Treating these cancers with minimally-invasive films could be a lot less dangerous than
deploying pharmaceutical chemicals."

Enticing tumor cells down a path of least resistance

The team had the idea of using nanofibers to treat glioblastoma because of work that had
already been done on making biomaterials to repair spinal cord injuries. There are similarities
in the work, for example the signaling pathways involved are the same.

Tumor cells usually invade healthy tissue by secreting enzymes to prepare the way. The cells
have to spend a lot of energy to make this happen. The researchers thought if they could offer the
cells a migration route where they did not have to spend a lot of energy, they would take
it.

First author Anjana Jain, assistant professor in the Department of Biomedical Engineering at
Worcester Polytechnic Institute in Massachusetts, who worked on the study when she was a
postdoctoral fellow in the Bellamkonda lab, says:

"Our idea was to give the tumor cells a path of least resistance, one that resembles the
natural structures in the brain, but is attractive because it does not require the cancer cells
to expend any more energy."

For the study, the team made nanofibers from polycaprolactone (PCL) polymer surrounded by a
polyurethane carrier. The surface of the material is very similar to the contours of blood
vessels and nerve fibers that the tumor cells travel along.

The researchers implanted the nanofibers into the brains of rats that had human
glioblastomas.

The team also treated other groups of rats for comparison. These were implanted with
nanofibers that had no PCL, or were made from untextured PCL film, or were untreated.

Treated rats showed significant glioblastoma tumor shrinkage

The tumor cells migrated along the nanofibers to a tumor collector outside the brain. The
tumor collector contained a gel with the drug cyclopamine, which is toxic to cancer cells.

After 18 days, the results showed that the rats treated with PCL nanofiber implants near the
tumors showed significant reductions in tumor sizes. Plus, their tumor cells had migrated along
the entire length of all nanofibers into the collector gel.

Prof. Bellamkonda says that while eradicating cancer would be ideal, an approach based on the
method they demonstrated might at least offer a way to control the growth of inoperable cancers,
and give patients a chance to live normal lives.

It will be some time before the technique moves from the lab into the clinic, maybe 10 years
or more, says the team.

Next steps include seeing how the method might work with other types of brain cancer and
cancers that are difficult to remove.

Funds from the National Cancer Institute of the National Institutes of Health (NIH) helped
finance the study.

Meanwhile, Medical News Today recently reported how researchers in Canada reactivated immune cells to treat
brain cancer. After treating diseased mice with a drug that reactivated immune cells that
are deactivated in glioblastoma, the animals lived two to three times longer.

My husband passed away 7 years ago from a Glioblastoma tumor. He died 5 months after his diagnosis at age 70. I do believe he had symptoms prior to going to the doctor but one night, I thought he was having a stroke because I couldn't make sense of his speech. It passed about 10 minutes later and he said it was like his thoughts were on an unraveling roll of toilet paper going very fast. We went to the hospital and they did a CT scan and said it looked like a mini stroke. About 15 days later, it happened again and the hospital told us to look for a neurologist. A week later, the tumor burst in his head on the way to the hospital. The doctor said he would operate to take the tumor out, but since it had burst, he would likely have a stroke because of the cleaning they would have to do in the brain. He did have a stroke and it affected his speech and comprehension and the whole left side of his body. He did have radiation and chemotherapy, but I would not have let them put him through that had I known he would not have survived anyway. As soon as the treatments began, he went downhill and was taken to the hospital several more times, getting worse and worse. In his case, because there was no cure, I would not treat with chemo or radiation if given the choice.

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